Hear from the authors of ‘High-throughput bioprinted 3D cultures for probing host-pathogen interactions in bioinspired microenvironments’

To celebrate the growth and development of the RSC Applied Polymers community and to highlight the remarkable authors who continue to contribute their high quality work to the journal, we would like to share the opinions and insights of these authors through this introductory blog post. Once dubbed #RSCAppliedfirst50, our blog posts aim to give a voice to the authors behind the research and hope that their insights might shed light upon growing challenges and progress in polymer science and its applications.

In this edition, we hear from Jodi Graf, DeVonte Moore, Catherine L. Grimes, Catherine A. Fromen and April M. Kloxin as they discuss their recently published article, ‘High-throughput bioprinted 3D cultures for probing host–pathogen interactions in bioinspired microenvironments‘.

 


An introduction from the authors

Cells in the human body respond not only to external chemicals, pathogens, or therapeutics, but also to the physical world surrounding them within tissues. The cellular microenvironment, composed of a matrix of biopolymers and neighboring cells, plays a pivotal role in shaping behavior. Seminal works have shown that matrix physical properties like stiffness, structure, and viscoelasticity can direct the fate and function of stem cells. However, less is known about how immune cells respond to such microenvironment cues in three dimensions as well as how these cues influence their response to ‘invaders’ like pathogenic bacteria.

Immune cells, especially macrophages, operate in complex, three-dimensional (3D) environments during infection and inflammation, yet these cells are often studied in hard, flat two-dimensional cultures on tissue culture plates, owing to their accessibility and high-throughput nature. What discoveries would be possible if well-defined 3D cultures of immune cells were widely available for high-throughput studies of responses to pathogens and other external stimuli? This important question – particularly how macrophages respond to bacterial pathogens in healthy to diseased 3D microenvironments – is what we aimed to address in this work. Addressing this question requires 3D biomaterial platforms that allow independent tuning of microenvironmental properties to systematically probe immune cell responses. We not only established high-throughput 3D immune cell culture workflows leveraging bioprinting, but also observed differences in the magnitude of both bacterial clearance and inflammatory responses across matrices with fibrotic-like versus healthy-like stiffness, highlighting how microenvironment properties can shape early immune responses.

This innovative work was enabled by collaboration with Inventia Life Science using the RASTRUM bioprinter. This bioprinter uses inkjet technology to rapidly create well-defined, synthetic extracellular matrices (ECMs) in a 96-well plate format, translating established hydrogel chemistries that we have used in different 3D culture models with a manual process to production at scale for accessible mechanistic studies and therapeutic screening. A full 96-well plate of 3D hydrogels for imaging can be printed in under 20 minutes, with a total time from start to finish of just 80 minutes. This partnership allows us to move from low-throughput, handcrafted models to scalable, reproducible 3D systems. We are excited to continue building complexity into these high-throughput, 3D culture models and to collaborate with the Inventia team to design tools and workflows that are accessible, translatable, and impactful for both academic and industrial labs.

If you are interested in learning more about our lab’s collaboration with Inventia, check out our YouTube video filmed and edited by the University of Delaware’s Office of Communications and Marketing. ​

Video link: Advanced 3D “bioprinters” help researchers find new disease treatments

 


Meet the authors

Jodi Graf

Jodi Graf is currently pursuing her PhD in the Chemical and Biomolecular Engineering Department at the University of Delaware, as a NSF Graduate Research Fellow. She is developing 3D in vitro models using biomaterials inspired by the microenvironment of the lung, under the supervision of Profs. April Kloxin and Catherine Fromen. She received her B.S. in chemical engineering from Lafayette College and worked as a downstream vaccine engineer for Merck & Co after college, before beginning her PhD at Univ. of Delaware. Her main research focus is understanding and modulating immune cell response to biomaterials.

 

 

 

 

 

 

DeVonte Moore

DeVonte Moore is a process scientist and lab manager at Merck, where he leads a dynamic team focusing on bioprocess scale-up towards vaccine and biologic commercialization. He earned his B.S. in chemistry from University of La Verne. He earned his Ph.D. from the University of Delaware under the supervision of Profs. April Kloxin and Catherine Grimes, where he utilized bioengineered 3D cell culture model systems to study disease mechanisms such as immune response to bacterial infection and breast cancer recurrence.

 

 

 

 

 

 

 

 

 

 

April M. Kloxin

April M. Kloxin, Ph.D., is the Director of the Delaware Biotechnology Institute, Associate Chair of Chemical and Biomolecular Engineering, and a Professor in the Departments of Chemical and Biomolecular Engineering, Materials Science and Engineering (joint), and Biomedical Engineering (affiliate) at the University of Delaware (UD), as well as a member of the Breast Cancer Research Program at the Helen F. Graham Cancer Center and Research Institute.  She obtained her B.S. and M.S. in Chemical Engineering from North Carolina State University and Ph.D. in Chemical Engineering from the University of Colorado, Boulder, as a NASA Graduate Student Research Program Fellow, and trained as a Howard Hughes Medical Institute Postdoctoral Research Associate at the University of Colorado, Boulder.  Her multi-disciplinary group creates unique materials with multiscale property control and applies them in conjunction with other innovative molecular tools for addressing outstanding problems in human health, with a focus on understanding and targeting dynamic cell-microenvironment interactions in wound healing, fibrosis, and cancer and translational systems for manufacturing and delivery of biologics and cell-based therapies. She is a member of the American Institute of Medical and Biological Engineering College of Fellows and recipient of the 2022 Mid-Career Faculty Excellence in Scholarship Award at the University of Delaware, the 2019 Biomaterials Science Lectureship, a 2018 ACS PMSE Arthur K. Doolittle Award, a NIH Director’s New Innovator Award, a Susan G. Komen Foundation Career Catalyst Research award, a NSF CAREER award, and a Pew Scholars in Biomedical Sciences award.

 

 

Catherine Fromen

Catherine Fromen, Ph.D., is the Centennial Term Professor for Excellence in Research and Education and an Associate Professor in the Departments of Chemical and Biomolecular Engineering and Biomedical Engineering at the University of Delaware. She received her Ph.D. in Chemical Engineering from North Carolina State University under the mentorship of Prof. Joseph DeSimone and completed her postdoctoral studies as a University of Michigan President’s Postdoctoral Fellow. Since joining the University of Delaware in 2017, Prof. Fromen has led innovative research on pulmonary engineering, focusing on engineering tools and therapeutics to address respiratory health challenges. Prof. Fromen serves as a board member of the International Society for Aerosols in Medicine (ISAM), a Learning Opportunity Manager for American Association of Pharmaceutical Scientists (AAPS) Inhalation and Nasal Community (INC) and was the 2025 ISAM Congress President. Her contributions have been recognized with prestigious awards recognizing her research and mentorship, including the Drug Delivery to the Lungs Emerging Scientist, AIChE 35 Under 35, NSF CAREER, NIH ESI MIRA, and AIChE Delaware Valley Section Outstanding Faculty Awards.

 

 

 

 

 

Catherine Leimkuhler Grimes

Catherine Leimkuhler Grimes, Ph.D., is Professor of Chemistry and Biological Sciences at the University of Delaware and Director of the NIH T32-funded Chemistry–Biology Interface training program. She earned her Ph.D. from Harvard University under Prof. Dan Kahne, where she synthesized glycopeptides to study antibiotic resistance, and completed postdoctoral training as a Howard Hughes Medical Institute and Cancer Research Institute Fellow at Harvard University and Massachusetts General Hospital.

Her research operates at the chemistry–materials–biology interface, developing carbohydrate- and peptidoglycan-inspired molecular tools to investigate bacterial cell wall architecture and bacteria–host immune interactions. Through the NIH Glycoscience Common Fund and an NIAID-funded P01, her group engineers chemical probes that enable mechanistic studies of infectious disease and immune recognition.

Her work has been recognized with awards including the ACS Infectious Diseases Young Investigator Award, Pew Biomedical Scholars Award, Alfred P. Sloan Research Fellowship, ACS Isbell Award, and Dreyfus Teacher-Scholar Award.

 

 

 

 

 


High-throughput bioprinted 3D cultures for probing host–pathogen interactions in bioinspired microenvironments

Jodi Graf, DeVonte Moore, Catherine L. Grimes, Catherine A. Fromen and April M. Kloxin

RSC Appl. Polym., 2026,4, 543-556. DOI: 10.1039/D5LP00285K

 


RSC Applied Polymers is a leading international journal for the application of polymers, including experimental and computational studies on both natural and synthetic systems. In this journal, you can discover cross-disciplinary scientific research that leverages polymeric materials in a range of applications. This includes high impact advances made possible with polymers across materials, biology, energy applications and beyond.